Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery

Yangzi Zhu, Meiyan Zhou, Xiuqin Jia, Wei Zhang, Yibing Shi, Shengjie Bai, Sanketh Rampes, Marcela P Vizcaychipi, Congyou Wu, Kai Wang, Daqing Ma, Qi Yang, Liwei Wang, Yangzi Zhu, Meiyan Zhou, Xiuqin Jia, Wei Zhang, Yibing Shi, Shengjie Bai, Sanketh Rampes, Marcela P Vizcaychipi, Congyou Wu, Kai Wang, Daqing Ma, Qi Yang, Liwei Wang

Abstract

Objective: To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation.

Background: Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear.

Methods: Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines.

Results: Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery.

Conclusions: The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

Conflict of interest statement

The authors report no conflicts of interest.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1
Figure 1
Neuropsychological assessment scores at baseline and at days 7 and 30 follow-ups in the 2 groups. A, The spider map shows that healthy controls did not have any significant changes in cognitive performance over a month. B, Surgery patients showed poor performance on the Corsi block, digit symbol, trail-making, pegboard (favored hand), and paired association learning tests on day 7 after cardiac surgery. These deficits were in remission on day 30 after cardiac surgery. For the trail-making test and pegboard test, the lower the scores are, the better the performance.
Figure 2
Figure 2
Positive and negative functional connectivity (FC) maps of the left DLPFC in healthy controls and surgery patients. A, Healthy controls. B, Surgery patients at baseline. C, Surgery patients on day 7 after cardiac surgery. D, Surgery patients on day 30 after cardiac surgery. The statistical threshold was P < 0.05. Colour bar indicates the t-value. DLPFC indicates dorsolateral prefrontal cortex.
Figure 3
Figure 3
Functional connectivity between groups and longitudinal changes within the surgery group. A, Axial view of significant clusters in the right DLPFC and AG. B, Axial view of significant clusters in the PCC. C, Axial view of significant clusters in the left SPL. D, The Lt. DLPFC showed increased connectivity with the right DLPFC from baseline to day 30 after cardiac surgery. E, The Lt.DLPFC showed decreased connectivity with the right Ag from baseline to day 30 after cardiac surgery. F, The Lt.DLPFC showed decreased negative connectivity with the PCC in the patients on day 7 after cardiac surgery compared with the healthy controls. G, The Lt.DLPFC showed decreased connectivity with the left SPL on day 7 after cardiac surgery compared to baseline. Data are presented as mean ± SD (control, n = 18; patients, n = 17). *P < 0.05, **P < 0.01, ***P < 0.001. AG indicates angular gyrus; Control, healthy controls; Lt.DLPFC, left dorsolateral prefrontal cortex; Post 7 d, day 7 follow-up after the operation; Post 30 d, day 30 follow-up after the operation; Pre, preoperation; SD, standard deviation.
Figure 4
Figure 4
Association between DLPFC connectivity and executive function in surgery patients on day 7 after surgery. A, The reduced negative connectivity between the Lt.DLPFC and AG was associated with higher scores on the trail-making test. B, The reduced negative connectivity between the Lt.DLPFC and PCC was associated with higher scores on the trail-making test. C, The increased connectivity between the bilateral DLPFC was associated with higher scores on the digit symbol test. D, The increased connectivity between the Lt.DLPFC and SPL was associated with lower scores on the pegboard (favored hand) test. For the pegboard and trail-making tests, higher scores indicate worse cognitive performance. AG indicates angular gyrus; Lt.DLPFC, left dorsolateral prefrontal; PCC, posterior cingulate; SPL, superior parietal lobule.
Figure 5
Figure 5
Plasma levels of TNF-α and IL-6 before and after surgery in surgery patients and healthy controls. A, Plasma levels of TNF-α in surgery patients were higher than those in healthy controls at baseline and further increased on day 7 after cardiac surgery before returning to near baseline on day 30 after cardiac surgery. B, The changes in the levels of IL-6 were similar to those of TNF-α in surgery patients. Data are presented as mean ± SD (control, n = 18; patients, n = 17). **P < 0.01. Control indicates healthy controls; IL-6, interleukin-6; Post 7 d, day 7 follow-up after the operation; Post 30 d, day 30 follow-up after the operation; Pre, preoperation; TNF-α, tumor necrosis factor-α; SD, standard deviation.
Figure 6
Figure 6
The relationships between TNF-α, Lt.DLPFC-PCC connectivity and executive function in 3 dimensions, based on multivariable linear regression models. Prediction of executive function by Lt.DLPFC-PCC connectivity and plasma levels of TNF-αon day 7 after surgery. Prediction of Lt.DLPFC-PCC connectivity by plasma levels of TNF-α on day 7 after surgery. Lt.DLPFC indicates left dorsolateral prefrontal; TNF- α, tumor necrosis factor-α.

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